Repa, Joyce , PhD
The vitamin D receptor and islet biology
General Research Subject: Type 2 Diabetes
Focus: Gene Chips and Microarrays, Integrated Physiology, Integrated Physiology\Insulin Secretion and Islet Hormones, Islet Biology, Islet Biology\Beta Cell Transcription Regulation
Type of Grant: Basic Science
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
Diabetes Type: Type 2 diabetes
Vitamin D has long been recognized for its importance in bone health and the regulation of serum calcium and phosphate levels. However, accumulating evidence suggests that Vitamin D may have a much broader role in physiology, affecting immune function, muscle strength, cancer progression and cardiovascular health. Several, albeit not all, epidemiological studies have implicated Vitamin D deficiency in the development of Type 2 Diabetes. First, the findings of some longitudinal observational studies suggest that individuals with low Vitamin D status have increased risk of developing Type 2 Diabetes. Secondly, the results of several small randomized trials of Vitamin D and glycemic outcome suggest that individuals with glucose intolerance or Type 2 Diabetes may benefit from Vitamin D supplementation. Finally, a single clinical study, reported to date, that assessed insulin secretion during a glucose tolerance test revealed a significant improvement in beta-cell function after 16 weeks of Vitamin D supplementation.
The most recent and comprehensive reviews of vitamin D and Type 2 diabetes: a meta-analysis of 18 prospective studies; and a scientific statement by the Endocrine Society, both conclude that more, carefully designed studies are needed to definitively conclude that Vitamin D may offer preventive or therapeutic benefit in type 2 diabetes. Preliminary data of this application demonstrate that vitamin D improves glucose-stimulated insulin secretion in mouse and human islets. Molecular analyses are underway to determine the mechanism of action for vitamin D in the beta-cells of the endocrine pancreas.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project covers research aimed to identify novel therapeutic targets to affect beta-cell function, primarily during the progression of type 2 diabetes mellitus.
My laboratory studies a family of hormone-activated transcription factors, which regulate gene expression to affect cell metabolism. We recently identified which of the 49 different members of this family of proteins are present in beta-cells, alpha-cells and islets of mouse and man. Among the most abundant of these factors, the Vitamin D receptor was identified, and studies in this particular project aim to determine the role(s) of vitamin D in beta-cell function, using genetic mouse models and cultured islets systems. Our goal is to detemine molecular pathways linking vitamin D status and the development/progression of type 2 diabetes.
If a person with diabetes were to ask you how your project will help them in the future,
how would you respond?
This research may aid in the development of new orally available drugs that promote survival and function of beta cells of the pancreas. These agents may allow for enhanced glucose responsiveness, proper insulin secretion and/or longer lifespan of the cells of the endocrine pancreas, thereby delaying or preventing the need for insulin therapy in type 2 diabetes mellitus.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Diabetes has become so prevalent in the last several years, that everyone (including myself and my laboratory personnel) has family, friends, and colleagues affected by this disease. It is our hope that our research will have a positive impact on understanding and treating diabetes.
In what direction do you see the future of diabetes research going?
With the completion of the human genome and the development of methods to assess the impact of drugs, nutrients, and disease states on gene expression, diabetes research will certainly move into and take advantage of this "genomics era". Hopefully, we will be able to use this new information in the design of appropriate strategies to prevent or treat diabetes.
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